Nanotechnology has great potential for development and application of novel chemical sensors and remediation approaches at Superfund and other toxic waste sites. However, nanomaterials may cause adverse health and environmental impacts during manufacturing, application, and disposal at the end of product life-cycle. A major concern in the emerging field of nanotoxicology is the analogy between commercial and noncommercial asbestos fibers and carbon nanotubes with respect to geometry, aspect ratio, rigidity, surface reactivity, and biopersistence. Identification of the fundamental physicochemical characteristics of nanomaterials relevant for their potential toxicity is required to prevent adverse health effects while retaining their unique properties for environmental sensing and remediation. An interdisciplinary research team at Brown University including a materials scientist, a toxicologic pathologist, and a molecular biologist has developed a panel of amphibole asbestos fibers, metallic nanoparticles, and carbon nanomaterials and innovative approaches for nanotoxicology assays. This panel of model nanomaterials will be expanded to include selected commercial materials subjected to rigorous characterization of toxicologically relevant materials properties. Carbon nanotubes are commercially produced in the presence of metal catalysts including Fe, Ni, or Y alone or in combination. The focus of this SBRP biomedical research project is on nickel-containing nanomaterials. Poorly-soluble nickel compounds are classified as known human carcinogens and nickel nanoparticles are highly toxic in short-term rodent lung toxicity assays. The proposed experiments will focus on the bioavailability and potential toxicity of nickel mobilized from metallic nickel nanoparticles and carbon nanotubes. The biochemical mechanisms responsible for acute toxicity of asproduced or purified commercial carbon nanotube samples will be assessed (Specific Aim 1). The potential synergistic or antagonistic effects of co-exposures to Ni plus Y catalyst residues will be assessed using human lung epithelial cells (Specific Aim 2). Finally, nickel-containing nanomaterials will be tested for activation of epigenetic pathways involved in nickel carcinogenesis (Specific Aims 3 and 4). These experiments will provide mechanistic information that will enable development of manufacturing methods and post processing steps to minimize or mitigate adverse health and environmental impacts of nanomaterials.